Vitamin A (Retinol)

 Vitamin A and its metabolites play diverse roles in physiology, ranging from incorporation into vision pigments to controlling transcription of a host of important genes. Health depends on maintaining vitamin A levels within a normal range, as either too little or too much of this vitamin lead to serious disease. 

Structure

Vitamin A or retinol has a structure depicted to the right. Retinol is the immediate precursor to two important active metabolites: retinal, which plays a critical role in vision, and retinoic acid, which serves as an intracellular messenger that affects transcription of a number of genes. Vitamin A does not occur in plants, but many plants contain carotenoids such as beta-carotene that can be converted to vitamin A within the intestine and other tissues. 

Physiologic Effects of Vitamin A

Vitamin A and its metabolites retinal and retinoic acid appear to serve a number of critical roles in physiology, as evidenced by the myriad of disorders that accompany deficiency or excess states. In many cases, precise mechanisms are poorly understood. Some of the well-characterized effects of vitamin A include:

• Vision: Retinal is a necessary structural component of rhodopsin or visual purple, the light sensitive pigment within rod and cone cells of the retina. If inadequate quantities of vitamin A are present, vision is impaired.
• Resistance to infectious disease: In almost every infectious disease studied, vitamin A deficiency has been shown to increase the frequency and severity of disease. Several large trials with malnourished children have demonstrated dramatic reductions in mortality from diseases such as measles by the simple and inexpensive procedure of providing vitamin A supplementation. This "anti-infective" effect is undoubtedly complex, but is due, in part, to the necessity for vitamin A in normal immune responses. Additionally, many infections are associated with inflammatory reactions that lead to reduced synthesis of retinol-binding protein and thus, reduced circulating levels of retinol.
• Epithelial cell "integrity": Many epithelial cells appear to require vitamin A for proper differentiation and maintenance. Lack of vitamin A leads to dysfunction of many epithelia - the skin becomes keratinized and scaly, and mucus secretion is suppressed. It seems likely that many of these effects are due to impaired transcriptional regulation due to deficits in retinoic acid signalling.
• Bone remodeling: Normal functioning of osteoblasts and osteoclasts is dependent upon vitamin A.
• Reproduction: Normal levels of vitamin A are required for sperm production, reflecting a requirement for vitamin A by spermatogenic epithelial (Sertoli) cells. Similarly, normal reproductive cycles in females require adequate availability of vitamin A.

Sources of Vitamin A

Vitamin A is present in many animal tissues, and is readily absorbed from such dietary sources in the terminal small intestine. Liver is clearly the richest dietary source of vitamin A.

Plants do not contain vitamin A, but many dark-green or dark-yellow plants (including the famous carrot) contain carotenoids such as beta-carotene that serve as provitamins because they are converted within the intestinal mucosa to retinol during absorption.

Vitamin A is stored in the liver as retinyl esters and, when needed, exported into blood, where it is carried by retinol binding protein for delivery to other tissues. 

Vitamin A Deficiency and Excess States

Both too much and too little vitamin A are well known causes of disease in man and animals.

Vitamin A deficiency usually results from malnutrition, but can also be due to abnormalities in intestinal absorption of retinol or carotenoids. Deficiency is prevalent in humans, especially children, in certain underdeveloped countries. In herbivores such as cattle, vitamin A deficiency is usually due to lack of green feed, such as in animals coming off of dry summer pastures or those fed poor quality hay. Because the liver stores rather large amounts of retinol, deficiency states typically take several months to develop. Some of the more serious manifestations of vitamin A deficiency include:

• Blindness due to inability to synthesize adequate quantities of rhodopsin. Moderate deficiency leads to deficits in vision under conditions of low light ("night blindness"), while severe deficiency can result in severe dryness and opacity of the cornea (xeropthalmia).
• Increased risk of mortality from infectious disease has been best studied in malnourished children, but also is seen in animals. In such cases, supplementation with vitamin A has been shown to substantially reduce mortality from diseases such as measles and gastrointestinal infections.
• Abnormal function of many epithelial cells, manifest by such diverse conditions as dry, scaly skin, inadequate secretion from mucosal surfaces, infertility, decreased synthesis of thyroid hormones and elevated cerebrospinal fluid pressure due to inadequate absorption in meninges.
• Abnormal bone growth in vitamin A-deficient animals can result in malformations and, when the skull is affected, disorders of the central nervous system and optic nerve.

Vitamin A excess states, while not as common as deficiency, also lead to disease. Vitamin A and most retinoids are highly toxic when taken in large amounts, and the most common cause of this disorder in both man and animals is excessive supplementation. In contrast, excessive intake of carotinoids are not reported to cause disease - you cannot use the excuse of potential vitamin A toxicity to avoid eating carrots or green vegetables!

 

Both hypovitaminosis A and hypervitaminosis A are known to cause congenital defects in animals and likely to have deleterious effects in humans. Pregnant women are advised not to take excessive vitamin A supplements, and some medical authorities also recommend that they consume liver only in moderation, which is usually not a hard sell to make.